Cancers are one of the leading causes of death in humans. The exact cause of cancer is not known. There is evidence that certain activities, such as smoking or exposure to carcinogens, may enhance the risk for certain types of cancers and tumors. Treatment of cancer in the early stages typically comprises local treatment such as, surgery and/or radiotherapy. While radiation therapy has been widely used in managing cancer, it is limited by lack of radiosensitivity of specific regions of malignant tumors. More advanced disease is treated by combining local treatment with chemotherapy. Although current chemotherapeutic agents have been shown to be effective against cancers and tumor cells, the use of combined treatment with all three modalities, surgery, radiotherapy, and chemotherapy, have not been shown to be effective against all cancer and tumor cells.
Significant effort in cancer therapeutics is also focused on cancers that are metastasized. About 40% of patients with advanced cancer develop metastases in the central nervous system, mainly from primary tumors of lung, breast and melanoma. In most cases there can be multiple CNS metastases, thereby adversely affecting surgery or localized radio-surgery. The current standard of care for these patients is radiation therapy, which can improve neurological symptoms but does not have any impact on patient's overall survival. Although over half of all cancer patients receive radiation therapy during treatment (Owen et al. Int J Radiat Oncol Biol Phys 24, 983-986, 1992), a need remains to improve the cure rate by radiation therapy alone. Radiotherapy has been the mainstay of treatment for most patients with unresectable brain metastases. Considering the time to non-CNS death, even in the case of uncontrolled primary and/or the presence of extracranial metastases, for selected patients (i.e. with Karnofsky Functional Index ≧70%) the outcome can be improved by achieving greater local control.
One approach to improve the intracranial control is to administer agents that enhance the sensitivity of cancer cells to irradiation. It has been surprisingly found that administering L-Arginine before radiation shows a surprising increase in tumor blood flowand decrease in glucose uptake, thereby decreasing tumor hypoxia and lactate production. This in turn can increase the tumoricidal effect of radiotherapy.